The long-term objective of this research is to shed light on how the cochlea analyzes sound. Others have demonstrated that single outer hair cells isolated in vitro change their longitudinal lengths in response to chemical or electrical stimuli. This and other data suggests that the outer hair cells play a role in the high sensitivity transduction process of the cochlea in response to sound and this has been included in several models. Our goal is to determine how chemicals such as neurotransmitters, modulators, and other chemicals present in the cochlea interact with the outer hair cells and alter their role in the transduction process. The hypothesis to be tested is that chemicals proposed as efferent neurotransmitters and neuromodulators and other chemicals in the cochlea react with receptors on the outer hair cells to produce one or more of the following changes in the outer hair cells: 1) length, and/or 2) ion channel activity, and/or 2) guanine nucleotide binding (G) protein activity. We will examine the mechanisms of any changes found by testing antagonists in addition to monitoring the effects of the chemicals on ion channel activity in the isolated hair cells. This information should aid researchers and physicians in identifying disease states which might involve malfunction of the outer hair cells in the processing of sound and in proposing drug intervention therapy.